PDHB
Basic information
Region (hg38): 3:58427630-58433857
Links
Phenotypes
GenCC
Source:
- pyruvate dehydrogenase E1-beta deficiency (Strong), mode of inheritance: AR
- pyruvate dehydrogenase E1-beta deficiency (Moderate), mode of inheritance: AR
- pyruvate dehydrogenase E1-beta deficiency (Strong), mode of inheritance: AR
- pyruvate dehydrogenase E1-beta deficiency (Supportive), mode of inheritance: AR
- Leigh syndrome (Moderate), mode of inheritance: AR
Clinical Genomic Database
Source:
Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
---|---|---|---|---|---|
Pyruvate dehydrogensae E1-beta deficiency | AR | General | Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing | Biochemical; Neurologic | 15138885; 21914562 |
ClinVar
This is a list of variants' phenotypes submitted to
- Pyruvate_dehydrogenase_E1-beta_deficiency (323 variants)
- Pyruvate_dehydrogenase_phosphatase_deficiency (28 variants)
- not_provided (27 variants)
- Inborn_genetic_diseases (22 variants)
- not_specified (17 variants)
- Pyruvate_dehydrogenase_complex_deficiency (16 variants)
- PDHB-related_disorder (1 variants)
- Seizure (1 variants)
- See_cases (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the PDHB gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000925.4. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
---|---|---|---|---|---|---|
synonymous | 134 | 139 | ||||
missense | 72 | 87 | ||||
nonsense | 8 | |||||
start loss | 1 | 1 | 2 | |||
frameshift | 14 | |||||
splice donor/acceptor (+/-2bp) | 7 | |||||
Total | 16 | 24 | 79 | 138 | 0 |
Highest pathogenic variant AF is 0.000237618
GnomAD
Source:
Gene | Type | Bio Type | Transcript | Coding Exons | Length |
---|---|---|---|---|---|
PDHB | protein_coding | protein_coding | ENST00000302746 | 10 | 6228 |
pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
---|---|---|---|---|---|---|
0.152 | 0.847 | 125734 | 0 | 14 | 125748 | 0.0000557 |
Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
---|---|---|---|---|---|---|
Missense | 1.57 | 139 | 202 | 0.690 | 0.00000975 | 2339 |
Missense in Polyphen | 37 | 86.725 | 0.42664 | 1048 | ||
Synonymous | -0.853 | 74 | 65.2 | 1.13 | 0.00000305 | 703 |
Loss of Function | 2.98 | 5 | 19.0 | 0.263 | 8.77e-7 | 232 |
LoF frequencies by population
Ethnicity | Sum of pLOFs | p |
---|---|---|
African & African-American | 0.0000579 | 0.0000579 |
Ashkenazi Jewish | 0.0000992 | 0.0000992 |
East Asian | 0.0000544 | 0.0000544 |
Finnish | 0.000139 | 0.000139 |
European (Non-Finnish) | 0.0000616 | 0.0000615 |
Middle Eastern | 0.0000544 | 0.0000544 |
South Asian | 0.00 | 0.00 |
Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle. {ECO:0000269|PubMed:17474719, ECO:0000269|PubMed:19081061}.;
- Disease
- DISEASE: Pyruvate dehydrogenase E1-beta deficiency (PDHBD) [MIM:614111]: An enzymatic defect causing primary lactic acidosis in children. It is associated with a broad clinical spectrum ranging from fatal lactic acidosis in the newborn to chronic neurologic dysfunction with structural abnormalities in the central nervous system without systemic acidosis. {ECO:0000269|PubMed:15138885}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Citrate cycle (TCA cycle) - Homo sapiens (human);Pyruvate metabolism - Homo sapiens (human);Glycolysis / Gluconeogenesis - Homo sapiens (human);Central carbon metabolism in cancer - Homo sapiens (human);HIF-1 signaling pathway - Homo sapiens (human);Glucagon signaling pathway - Homo sapiens (human);Warburg Effect;Pyruvate Dehydrogenase Complex Deficiency;Transfer of Acetyl Groups into Mitochondria;The oncogenic action of Succinate;The oncogenic action of Fumarate;Primary hyperoxaluria II, PH2;Pyruvate kinase deficiency;Pyruvate dehydrogenase deficiency (E3);Pyruvate dehydrogenase deficiency (E2);2-ketoglutarate dehydrogenase complex deficiency;Mitochondrial complex II deficiency;Fumarase deficiency;Congenital lactic acidosis;Citric Acid Cycle;Leigh Syndrome;Glutaminolysis and Cancer;The oncogenic action of 2-hydroxyglutarate;Pyruvate Metabolism;The oncogenic action of L-2-hydroxyglutarate in Hydroxygluaricaciduria;The oncogenic action of D-2-hydroxyglutarate in Hydroxygluaricaciduria ;Pyruvate Decarboxylase E1 Component Deficiency (PDHE1 Deficiency);Hereditary Leiomyomatosis and Renal Cell Carcinoma Pathway;Glycolysis and Gluconeogenesis;Signal Transduction;Regulation of pyruvate dehydrogenase (PDH) complex;Pyruvate metabolism;Pyruvate metabolism and Citric Acid (TCA) cycle;Metabolism of amino acids and derivatives;The citric acid (TCA) cycle and respiratory electron transport;Glycolysis and Gluconeogenesis;Metabolism;pyruvate decarboxylation to acetyl CoA;Glyoxylate metabolism and glycine degradation;Pyruvate metabolism;Signaling by Retinoic Acid;Signaling by Nuclear Receptors;superpathway of conversion of glucose to acetyl CoA and entry into the TCA cycle
(Consensus)
Recessive Scores
- pRec
- 0.447
Intolerance Scores
- loftool
- 0.124
- rvis_EVS
- -0.41
- rvis_percentile_EVS
- 26.23
Haploinsufficiency Scores
- pHI
- 0.393
- hipred
- Y
- hipred_score
- 0.685
- ghis
- 0.658
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.990
Gene Damage Prediction
All | Recessive | Dominant | |
---|---|---|---|
Mendelian | Medium | Medium | Medium |
Primary Immunodeficiency | Medium | Medium | Medium |
Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Pdhb
- Phenotype
Zebrafish Information Network
- Gene name
- pdhb
- Affected structure
- amacrine cell
- Phenotype tag
- abnormal
- Phenotype quality
- decreased amount
Gene ontology
- Biological process
- glucose metabolic process;acetyl-CoA biosynthetic process from pyruvate;tricarboxylic acid cycle;mitochondrial acetyl-CoA biosynthetic process from pyruvate
- Cellular component
- nucleus;nucleoplasm;mitochondrion;mitochondrial matrix;pyruvate dehydrogenase complex
- Molecular function
- pyruvate dehydrogenase activity;pyruvate dehydrogenase (acetyl-transferring) activity;protein binding;pyruvate dehydrogenase (NAD+) activity